The proposed work concerns the chemical mechanism and physiological control of malic enzyme and fatty acid synthetase, two key enzymes involved in the de novo biosynthesis of fatty acids in living organisms. Fatty acid synthetase is a multienzyme complex composed of at least 7-8 enzyme components. Our goal is to delineate the spatial arrangement of enzyme components as well as the non-identical half-size subcomplexes in this highly organized molecule, and to ultimately decipher the chemical mechanism and regulation of each enzyme component. Malic enzyme functions to provide reducing equivalents for fatty acid synthesis. It is a bifunctional enzyme capable of catalyzing both NADP ion linked hydride transfer and c-c bond cleavage reactions. This enzyme contains a sulfhydryl group at the active center which is specifically modified by selected chemical reagents. The use of structurally dissimilar reagents enables us to probe the microenvironment surrounding this -SH residue. We are also looking at the interaction of this enzyme with its metal cofactor Mn ion.